This invention relates to radiopaque polyurethane compositions having a bromine content of at least 15% by weight prepared by the reaction of cycloaliphatic diisocyanates, certain polyether diols, and a sufficient amount of tetrabromodipentaerythritol or a mixture thereof with dibromoneopentyl glycol to provide the required bromine content.
When medical or veterinary devices are inserted or implanted in a subject, it is often desirable to be able to locate them by X-ray examination, particularly when catheters or cannulas are being inserted into body cavities, passages, or vessels. It is also often desirable, especially with catheters, to observe visually fluids within exposed portions of such devices.
Consequently, an object of the present invention is to prepare radiopaque polyurethane compositions that are optically transparent.
Several approaches for achieving this object in catheters have been reported. For example, U.S. Pat. No. 2,212,334 discloses the incorporation of short segments of radiopaque material within otherwise transparent tubes by introduction of such material at regular intervals during manufacture of the catheters. Alternatively, U.S. Pat. Nos. 2,857,915, 4,027,659, and 4,105,732 disclose the introduction of the radiopaque material as continuous stripes running the length of the catheters. It is also possible to include a radiopaque material only at the distal end of the catheter, as disclosed in U.S. Pat. No. 3,605,750, but the intervening portion of the catheter is not readily detectable by X-ray examination. Similarly, U.S. Pat. No. 3,529,633 discloses catheters made primarily from polymers that are opaque to both X-rays and visible light but also have small sections made from transparent materials.
Another variant of this approach is described in U.S. Pat. No. 3,618,614, which discloses a multiwall tubing having a thick transparent inner tube encased within a thin transparent tube containing a radiopaque material. In this variant, the relatively longer pathlength through edges of the tube provides sufficient contrast to appear during X-ray examination. U.S. Pat. No. 3,336,918 discloses similar effects obtained by incorporating metal powders into polyurethane coatings.
Yet another approach is to disperse X-ray opaque substances, such as barium sulfate, a bismuth halide, or a halogen-containing plasticizer, diol, or other such halogen-containing material, throughout a visually transparent polymer. See, for example, Y. Delaviz et al., Polymer Preprints (Polymer Division, Am. Chem. Soc.), 30, 215-216 (1989), and U.S. Pat. Nos. 3,608,555, 3,645,955, 3,749,134, 3,901,829, and 4,282,876. Blends of polymers, at least one of which is radiopaque, are reported, for example, in U.S. Pat. No. 4,182,787, to provide similar effects. Each of these approaches, however, involves the use of physical blends, at least some of which have inherent disadvantages. For example, some of the radiopaque substances can be leached out of the polymeric substrate and absorbed by the body. In addition, some additives can have other incompatibilities that make them unsuitable for use in humans or animals.
It would be particularly advantageous to make the medical or veterinary devices from a polymeric material in which the radiopaque component is incorporated as a structural unit of the polymer. For example, U.S. Pat. No. 4,722,344, which is incorporated by reference, discloses polyurethanes prepared using halogenated polyols and/or halogenated polyisocyanates as reactants. Although the polyurethanes disclosed in U.S. Pat. No. 4,722,344 incorporate sufficient bromine to provide the desired radiopacity, these polyurethanes have a high flex modulus and are not as soft as desired under saline conditions (such as typical of blood). For example, when using a chain extender such as dibromoneopentyl glycol, the desired bromine content (about 25% of the weight of polyurethane) can be achieved only by using a relatively large quantity of the chain extender, which results in a comparatively large hard segment content (i.e., the sum of the amounts of the low molecular weight chain extender and polyisocyanate components) relative to the soft segment content (i.e., the amount of the higher molecular weight polyol component). During use, such relatively hard polyurethanes could irritate tissues with which they are in contact. In addition, even slightly rough surfaces could increase the possibility of transporting bacteria into the body, particularly skin bacteria contacted at the point of entry into the body. The polyurethane can be softened by known methods, for example, by introducing hydrophilic structural units such as non-ionic groups (e.g., polyoxyethylene groups) or ionic groups, but such methods would undesirably reduce the bromine content and could adversely affect various physical properties of the polyurethane.
It was, therefore, an object of the present invention to obtain optically transparent radiopaque polyurethanes that have high halogen content but which are soft, especially under physiological conditions. This object has been accomplished by partially or completely replacing the previously reported brominated chain extenders with tetrabromodipentaerythritol.